Essential thrombocythemia (ET)

Essential thrombocythemia (ET) is one of the myeloproliferative, BCR::ABL1-negative neoplasms (MPN). It is characterized by a persistent increase in platelet count and an increased number of large, mature megakaryocytes in the bone marrow, resulting in the risk of thrombosis and/or bleeding. Due to the lack of specific markers, the diagnosis is not always clear, which is why secondary thrombocytosis should always be excluded for differential diagnosis.

ET is usually diagnosed within the chronic phase. In a small number of patients, ET progresses to the accelerated phase and blast phase, which are diagnosed when the blast percentage in the bone marrow or peripheral blood is 10-19% (accelerated phase) or ≥20% (blast phase). Although many patients remain asymptomatic, disease progression to myelofibrosis and/or acute myeloid leukemia may also occur (WHO 2022).

Clinical differentiation within BCR::ABL1-negative myeloproliferative neoplasms is based, among other things, on the detection of clonal thrombocytosis (Table 1). In peripheral blood smears, platelets are morphologically altered in 90% of patients: enlarged and/or variable in size. However, it should be noted that there are currently no specific disease markers that unequivocally diagnose ET, which is why a diagnosis should always be made based on a combination of clinical, molecular genetic and bone marrow histological findings.

Within the chronic myeloproliferative diseases, ET shows the most favorable course. Affected patients usually have a normal life expectancy, but there is an increased risk of thrombosis and a higher incidence of thrombotic events after the first decade (Elliott & Tefferi 2005, Wolanskyj et al. 2006). Therapy selection involves categorizing patients based on their risk for vascular complications. A comprehensive treatment approach would include complete cardiovascular risk assessment and monitoring (Godfrey et al. 2023). Transformation to blast phase or MDS occurs in less than 5% of cases and is likely associated with prior cytotoxic therapy (WHO 2022). Most prognostic systems are based on the identification of risk factors (thromboembolic complications or major bleeding, age ≥60 years, platelets ≥1.5 million/µl) that allow early identification of patients at risk of thrombosis and bleeding. An overview of this can be found in the Onkopedia guideline Essential (or Primary) Thrombocythemia. Newer scores such as the IPSET (International Prognostic Score for Thrombosis in Essential Thrombocythemia) additionally take into account cardiovascular risk factors and the presence of a JAK2 V617F mutation (Barbui et al. 2012, Haider et al. 2016). Patients with a CALR mutation show a lower risk of thrombosis compared with patients with a JAK2 mutation (Torregrosa et al. 2016).

Even "non-driver mutations" can have an impact on prognosis (Table 3) and are used, for example, in the MIPSS-ET (mutation-enhanced international prognostic system for essential thrombocythaemia) (Tefferi et al. 2020).

There is currently no known curative therapy for ET, so the goals of therapy are to reduce disease-related symptoms and complications and to reduce the risk of thromboembolism and cardiovascular risk factors. An overview of therapeutic regimens is provided in the Onkopedia guideline Essential (or Primary) Thrombocythemia. A review of selected therapeutics already approved or in clinical development for MPNs is also available in a summary by How et al (How et al. 2023).